Top Banner
Protein Design Based on the Designability of Protein Structures Chen Zeng, PI (GWU) Chao Tang, Co-PI (NEC) Ned Wingreen (Princeton) Naigong Zhang (GWU) Luhua Lai (PKU) NSF Support: DMR-0094176, 0313129
13

Protein Design Based on the Designability of Protein Structures

Dec 31, 2015

Download

Documents

Protein Design Based on the Designability of Protein Structures. Chen Zeng, PI (GWU) Chao Tang, Co-PI (NEC) Ned Wingreen (Princeton) Naigong Zhang (GWU) Luhua Lai (PKU) NSF Support: DMR-0094176, 0313129. Protein Folds (~1000! Why so small?). Acylphosphatase. Ribosomal protein S6. - PowerPoint PPT Presentation
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Page 1: Protein Design Based on the Designability of Protein Structures

Protein Design Based on the Designability of Protein Structures

Chen Zeng, PI (GWU)

Chao Tang, Co-PI (NEC)

Ned Wingreen (Princeton)

Naigong Zhang (GWU)

Luhua Lai (PKU)

NSF Support:DMR-0094176, 0313129

Page 2: Protein Design Based on the Designability of Protein Structures

Protein Folds (~1000! Why so small?)

Acylphosphatase

Viral DNA-binding domain

Ribosomal protein S6

Ferredoxin

Page 3: Protein Design Based on the Designability of Protein Structures

HP Lattice Model

EHH

EHP

EPP

,

( )i j i j

i j

H E r r

2.3

1

0

HH

HP

PP

E

E

E

2HH HP PP

HH PP HP

E E E

E E E

H--Hydrophobic

P--Polar(Dill)

HydrophobicitySegregation

Page 4: Protein Design Based on the Designability of Protein Structures

Enumeration (HP Lattice Model) H. Li, C. Tang, N. Wingreen (NEC)

Designability

NS=1

NS=5

NS=0

NS=2

NS=1

95% sequences havedegenerate G-states

Sequences (108) Structures (105)

Page 5: Protein Design Based on the Designability of Protein Structures

Top Lattice Structures

Page 6: Protein Design Based on the Designability of Protein Structures

…, mm

Off-Lattice m-State ModelPark & Levitt (1995)

Page 7: Protein Design Based on the Designability of Protein Structures

Fit to 1PSV By 3-State Model

crms ~ 0.8 Ao

1PSV

Page 8: Protein Design Based on the Designability of Protein Structures

Enumeration of Configurations (off-lattice HP model)

ai – accessible surface area of residue i

A= ai < Ac

H = hi a’i (a’i=ai/A)

Page 9: Protein Design Based on the Designability of Protein Structures

Searching for New Folds

MAQTDVILCPDTHQKAVCLEKIR EYFDCGLPSAQWCVIKNALLTFRPNMDKILYVVACQGGARASLTLRGAWETRKLHCMQPIVYTTLNGLTMNSAKPLVVTIYSQYNVHLRFDDGFDSKLACVNPMRTYEIWLETFRMLKSPQCNYIAVRIHGRYLDFGSCVNKMYHGFDAALLTRQVLPSLTQIVLTAGNYIGRGPNIPCLDIGSEFIINCAQLVRENHWGVSGLRANLAGTRVNIMPCDEWSILSLMKIHFHDISAQVYTERPQMVKRLAFRATCNMRWDPSIVYTWQFGHLCVHEWMTVINEDSAPILCWHGGLMFGNVVEERPAADIMNWGLRCSLKELTILKNETVGGAPQWYIVHNQFNAKNQKDIETRYPMKSLVSCILHIKMLMKIHYDTFREWQVNSCKLDDVSMSKALLVPQWIVRCSYTPLKWPSTCNMRWDPSIVYTWQFGHLSLVTCAKVINEDSAPILCTRSGLRLTDVNYIPPAADIAQREMRCSLTNQLVDGHETVGGAPQWYFAKRLCRGADEYLIETRYPMKSLILSTAEEKLATDIHYDAGREWQVNSFELITSVETLDLLVPQWIVRCSHTFDIPQS

Page 10: Protein Design Based on the Designability of Protein Structures

N=23, r=1.9 A, =0.4 A, 10,000 configurations, 4688 clusters

o o

Histogram of Ns

Page 11: Protein Design Based on the Designability of Protein Structures

Energy gap vs. Ns

Page 12: Protein Design Based on the Designability of Protein Structures

Design Procedure

II. Pick Top Folds

III. Sequence Design and Verification

I. Model Computation

motif

2nac 2bnh

Page 13: Protein Design Based on the Designability of Protein Structures

Design Protocol